Fluids/Electrolytes/Acid/Base Flashcards

1
Q

Definition of Electrolyte

A

POS or NEG Charged molecules that give off ions when dissolved in H2O

Cation = POS
Anion = NEG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Extracellular fluid

#3, how much contributes to TBW?
how is ECF divided?

A
  1. space w/i intravascular blood vessels = 4%
  2. Interstitial fluid w/i tissue = 15%
  3. Transcellular = 1%
    * bile, CSF, synovial, glandular

Interstitial is 75% of ECF
Intravascular is 25% of ECF

Total = 1/3 total body water (approx 20% of bw)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Intracellular Fluid

#3, how much contributes to TBW?

A
  1. Space w/i the cells and fluid
  2. Gives shape/form/functionality
  3. Largest Volume of fluid in the body is INTRACELLULAR

Total = 2/3 of total body water (approx. 40% bw)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define:

Solutes
Ions
Electrolytes

A
  1. water w/ dissolved substances w/i all body compartments
  2. POS or NEG charged molecules
  3. Substances given off when dissolved in water from ions → Na+/K+/Cl-/Ca++/Mg++/Phos
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Na+/K+ ATPase Pump

A

Intracellular Pump that ensures Na+ gets removed from cell and K+ stays intracellular
* majority of Na+ extracellular → 140meq/L ECF (pulls Cl- with)
* Majority of K+ intracellular (140meq/L ICF)

Ex: Beta Blockers → propanolol blocks Na+/K+ ATP pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Intracellular Cation and Anions

A

Cations = K+ Mg++
Anions = Phos (needed for ATP and to bind to glucose)
* Blood proteins (mainly NEG charged)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Extracellular Cations and Anions

A

Cations = Ca++, Na+ (Na+/K+ pump)
Anions = Cl- → net from Na+/K+ pump
* HCO3- →ECF reserves are alkaline to buffer acids inside the cell
* Cl- → follows Na+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Anion Gap

A

Difference between measured Cations and anions in the blood
–numerous unmeasured anions = ↑
anion gap to maintain zero net electric plasma charge (Cations and Anions must always equal)

Normal K9= 10-24 mmol/L Fel= 13-27 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

7

Examples of unmeasured Anions

A

Lactate
Ketones
Ethylene glycol
Uremia
Aspirins
Alcohols
cyanide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

OsmolARITY

A

concentration of a solution expressed as mOsm/L

LAR=LITER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

OsmolALITY

A

concentration of a solution expressed as mOsm/kg

Normal = K9 = 290-310 mOsm/kg Fel= 290-330 mOsm/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Tonicity

3 types

A

Ability of extracellular solutions to move water in or out of cell via osmosis
Isotonic = do not cause changes in h20 movement across cell membrane
Hypotonic = tonicity LESS than plasma causes H2O to move INTO cells
Hypertonic = tonicity HIGHER than plasma, causes fluid to move OUT of cells into fluid

“effective osmolality”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Osmotic Pressure

Definition
Effects of HyperNa+ and HypONa+ on water

A

Pressure needed applied to H20 to prevent osmosis (movement of water)

HyperNa+ → cells volume loss due to osmotic gradient pushing water into hyperosmolar extracellular space
HypoNa+ → cells SWELL as H2O gets pushed into cells

Ex: Na+ and Glucose

WATER FOLLOWS Na+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Ca++ ATP pump

What is it exchanged for?
Which system utilizes this?

A

Ca++ moves outside cell when Na+ shifts intracellularly
“couter-transport”
– enters the plasma by absorption from the gastrointestinal tract regulated by vitamin D and by resorption from the bones.
– leaves the plasma by secretion into GIT, urinary excretion, and deposition into bones
–important for muscle activity/contrations
–nerve impulse transmissions
–blood clotting

Ex: Digoxin → inhibits Na+/K+ ATP exchange, Na+ stays in ECS → Ca++ stays ICS for contractility improvement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

H+ ATPase pump

A

– H+-K+-ATPases are ion pumps that use the energy of ATP hydrolysis to transport protons (H+) in exchange for (K+).
– Dumps acid ASAP in metabolic acidosis

Proximal Convuluted tubule in Kidney

HCO3 is later reabsorbed as buffer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Free water deficit definition

A

–determines the volume (L) of water required to correct dehydration or, to reach the desired level of sodium in the blood serum
Does Not Follow Lytes
H2O w/o solutes
–Kidney depends on Free H2O to concentrate/dilute urine influenced by ADH
–Deficits occur w/ solute-free water loss from body

2nd to CKD/D+/V+/Panc/Peritonitist/FBO/DI/Adipsia/Lack of water access

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Law of Electroneutrality

A

any single ionic solution, sum of negative charges attracts an equal sum of positive chargers concentration of cations = concentration of anions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Na+ review

Normal vs Disturbances

A

Normal actions: TBW inverse relation with Na+
–fluid regulation
osmosis → H2O FOLLOWS Na+
Distrubances: cells shrink or swells w/i brain → mental abnormalities
–free water deficit
–toxicity (play dough)
–sz/ataxia/behavioral changes/lethargy

Main Na+ ECF cation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

K+ Review

Normal vs Disturbances

A

Normal actions: resting membrane potential → needed for action potential and repolarization of myocaridal cells
–absorbed in SI/excreted by kidneys and colon
Disturbances: membrane potential problems → arrhythmias
–affected by acid-base disturbances → low pH = high K+; high pH = low K+
–affected by lack of insulin
–Reperfusion syndrome → increase in insulin stimulates intracellular uptake of K+/phos-
–bradycardia/tall T-waves/ Small P-waves

Intracellular cation (99%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Ca++ Review

Normal vs Disturbances

where is it stored?
What regulates it?

A

Normal actions: stored in bones; absorbed thru diet

– HypOCa++ = ↑ permeability to Na+ → action potential = ↑↑ excitability
– HypERCa++= ↓ permeability to Na+ = ↓ action potential = ↓↓ excitability
–PTH controls ECF Ca++ (and Phos) Calicitonin via C-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mg++ Review

Normal vs Disturbances

where is it stored/absorded?
what transports is it apart of?

A

Normal actions: stored in bones/absorbed in SI
–affects active transport or Na+/K+ ATP pump
–blocks Ca++ channels intracellularly
Disturbances: Nerve/muscle problems → twitching/ faciculations
–arrhythmias
–associated with other lyte derangements → refractory hyPOCa++/hyPO K+ (active transport)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Cl- Review

Normal vs Disturbances

Where is it absorbed? What is it reguated by?

A

Normal actions: Needed for acid/base balance
–absorbed from diet
–regulated by kidney
Disturbances: associated with body water disturbances
–will cause opposite changes to HCO3 → hyPO will raise, hyPER will lower
– ↓ with GI losses

Major Extracellular Anion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Phos Review

Normal vs Disturbances

What is responsible for regulating it?

A

Normal actions: absorbed/excreted along with Ca++
–Mineral for bone strength
–ATP phos bond carries energy for ALL CELL functions
–buffers bone/serum/urine
Disturbances: ↑ PTH = ↑ Ca++ = ↑ Phos excreted = hyPOphos
– ↓ GFR = ↓ Phos excreted =hypERphos
–Insulin causes Phos to shift intracellularly
–Refeeding syndrome

Major intracellular Anion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

5

ECF Osmoles

A

Na+
Glucose
Urea
K+
Cl-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Effective vs Ineffective osmoles | Examples of each How do they affect water movement?
**Effective:** Do not freely cross cell membrane → Na+/Glu/K+ * Na+/K+ pump is what moves molecules across membrane **Ineffective:** Freely crosses cell membrane → Urea (cannot create osmotic gradient) ## Footnote Retention incites H2O to cross membrane toward side w/ higher concentration of effective osmoles
26
Na+/Glu Co-Transporter
responsible for maximizing the absorption of glucose from the intestinal tract and the recovery of glucose from the proximal tubule of the kidney following glomerular filtration | Facillitated diffusion *Glu follows Na+
27
Na+/H+ Exchange
--Na+ is exchanged for H+ (Na+ **IN** H+ **OUT**) → PCT --Utilized during metabolic acidosis ## Footnote PCT → CO2 + H2O = H2CO3 (carbonic acid) → HCO3 + H+ (**bicarb get reabsorbed in peritubule capillary** and **H+ gets excreted in distal convuluted tubule**
28
Obligated Water ## Footnote Example, what is responsible for reabsorption?
Obligated to follow Electrolytes --H2O obligated to follow Na+ -- Aldosterone responsible for reabsorbing obligated water
29
HCO3/Cl- Transporter
--HCO3 is exchanged for Cl-
30
Na+ Regulators Absorption Excretion
--Thirst/AldosteroneADH main regulators --absorbed in PCT/ALOH via carrier protein --cotransport of Glu/AA --exchanged for H+/ammonium/K+ when reabsorbed
31
K+ Regulators Absorption Excretion
--Reabsorped in PCT/ALOH/DCT
32
H+ Absorption Excretion
--PCT H+ is sent out in exchanged for Na+ --DCT H+ →Alpha intercalated cells use ATP to pump H+ into urine --Ammonium combines with H+ in DCT to become a weak acid (keep urine pH from dropping too low)
33
Renal buffer system
homeostatic mechanism that uses the kidneys to help maintain the acid-base balance by excreting either an acidic or alkaline urine in response to changes in the hydrogen ion concentration of body fluids. Renal buffering involves a complex series of reactions within kidney tubules.
34
Osmolar Gap
Measure - Calculated --does not exist just missing pieces of the equation! | If difference > 10 there is a problem
35
Osmosis
movement of water from a high concentration to a low concentration --membrane permeable to WATER not the SOLUTES | Na+ is KING of osmosis
36
Interstital Fluid
formed by filtration of fluid out of microvessels and removed via the lymphatic system or transudation across the serosal surface of the organ
37
Interstitial fluid pressure ## Footnote what does it mediate? what does it inhibit? what is it dependent on?
-- responsible for mediating the balance between microvascular filtration and the two interstitial outflows -- ↑= inhibits filtration and promotes lymph flow and serosal transudation -- interstitial fluid volume dependent on pressure and its relationship with the current volume
38
Microvascular filtration ## Footnote What is it comprised of? what directly effects it?
-- Endothelial glycocalyx is primarily the barrier to microvascular filtration -- COP of fluid on the interstitial side of the glycocalyx and w/i endothelial clefts has more direct effect on filtration than that of bulk interstitial fluid
39
What is the glycocalyx comprised of?
glycoproteins, proteoglycans, and glycosaminoglycans that form a layer attached to the luminal surface of vascular endothelial cells
40
Starling-Landis equation
-- direction of microvascular filtration depends on the **sum of the hydrostatic and colloid osmotic pressure gradients** -- magnitude of filtration is the **product of the hydraulic conductivity, surface area, and net pressure gradient.**
41
COP of plasma
-- consequence of the concentration of proteins, particularly albumin, as well as the redistribution of permeable ions induced by the presence of charges on those proteins
42
Lymphatic drainage ## Footnote Where does this start and end? Where is this utilized?
Removes interstitial fluid and returns it to the venous blood -- begins with terminal lymphatic vessels w/i interstitial space → larger vessels through lymph nodes, → terminates in the venous system --Pleural fluid and peritoneal fluid removed by lymphatic drainage to return to venous circulation
43
What factors regulate Lymph flow? | #7
modified by numerous vasoactive mediators: prostaglandins thromboxane nitric oxide epinephrine acetylcholine substance P - neurotransmitter and a neuromodulator bradykinin - peptide that promotes inflammation
44
What do lymphatic vessels respond to?
-- increased outflow pressure by increasing pumping activity via increases in the strength and frequency of contractions.
45
Serosal transudation
Edema-induced increases in **interstitial hydrostatic pressure will increase the rate of transudation** and may result in **effusion within the surrounding cavity of suspended organs**
46
Antiedema mechanisms | #4
intrinsic interdependent mechanisms include: (1) increased interstitial hydrostatic pressure (2) increased lymph flow (3) decreased interstitial colloid osmotic pressure (4) increased trans-serosal flow in organs within potential spaces ## Footnote they incur little energy cost and are effective because they respond rapidly to edema formation
47
Mechanisms of edema formation ## Footnote x5
1. **Venous hypertension** → Increased microvascular pressure and filtration 2. **Hypoproteinemia** → Decreased plasma colloid osmotic pressure, increased filtration 3. **Increased microvascular permeability** → Increased filtration 4. **Impaired lymph flow** →Vessel obstruction or damage 5. **Increased negativity of interstitial fluid pressure** → Shift in interstitial pressure–volume relationship, decreased interstitial pressure
48
Regulation of plasma osmolality | What mechanisms regulate plasma osmolality?
**Hypothalamic osmoreceptors** sense changes in plasma osmolality, and changes of only 2–3 mOsm/L induce compensatory mechanisms to return the plasma osmolality to its hypothalamic setpoint -- two major physiologic mechanisms for controlling plasma osmolality are the antidiuretic hormone (ADH) system and thirst
49
ADH | Definition, where does it come from? What is it stimulated by?
ADH is a small peptide secreted by the posterior pituitary gland Stimulated by: -- elevated plasma osmolality -- decreased effective circulating volume.
50
Osmoreceptors | How to do they stimulate ADH release?
Specialized group of cells in the **hypothalamus** -- with ↑ plasma osmolality = cell shrinkage → send impulses via neural afferents to the **posterior pituitary → stimulate ADH release**
51
How is ADH stimulated by low circulating volume? | How does it fix it?
When effective circulating volume is low, baroreceptor cells in the **aortic arch and carotid bodies** send neural impulses to the pituitary gland that stimulate ADH release -- H2o crosses into the hyperosmolar renal medullary interstitium and into the vasa recta along its osmotic gradient; the H2o is then returned to the general circulation
52
Aquaporin channels
Aquaporins are channels that allow water to move from the tubular lumen into the renal tubular cell
53
ADH effect on Aquaporin channels ## Footnote What receptor does it activate?
When ADH activates the V2 receptor on the renal collecting tubular cell, aquaporin-2 molecules insert into the cell’s luminal membrane
54
Lack of ADH in Renal tubular collecting ducts =
become impermeable to water
55
Hyperosmolality effect on Thirst
Stimulate thirst -- The mechanisms by which hyperosmolality and hypovolemia stimulate thirst are similar to those that stimulate ADH release
56
Role of RAAS and ADH for effective circulation volume regulation
RAAS = monitors and fine-tunes effective circulating volume ADH system maintains normal plasma osmolality
57
Which is more important effective Circulating volume or plasma osmolality?
maintenance of effective circulating volume is prioritized over maintenance of normal plasma osmolality, so in patients with poor effective circulating volume, thirst and ADH release increase irrespective of plasma osmolality
58
How does an increase in water intake affect Na+?
increased water intake (from drinking) and water retention (from ADH action at the level of the kidney) decrease plasma [Na+] and can lead to hyponatremia (and thus hypoosmolality) in patients with poor effective circulating volume ## Footnote Ex: Chronic heart failure patient with hyponatremia
59
Total body sodium content versus plasma sodium concentration
Plasma Na+ concentration independent from TB Na+ content TB Na+ content = total # of sodium molecules in the body, regardless of the ratio of sodium molecules to water molecules.
60
How is Hydration status determined?
Na+ content determines the hydration status of the animal -- dehydrated, euhydrated, overhydrated
61
Overhydration
-- **increased total body sodium** -- increased quantity of fluid is maintained within the interstitial space and the animal appears overhydrated, regardless of the [Na+].
62
Dehydration
-- **decreased total body sodium content** --decreased quantity of fluid is maintained within the interstitial space and the animal appears dehydrated, regardless of the [Na+]. -- **hypovolemia occurs because fluid moves from IVS into the interstitial space** -- as a result of **decreased interstitial hydrostatic pressure = fluid deficit in the intravascular space**
63
Cause for hyperNa+ : Water deficit – excessive water loss | #5
1. Renal water loss 2. Osmotic diuresis due to glucosuria or mannitol causes an electrolyte-free water loss = hyperNa+ in sick animals with no water access 3. Diabetes insipidus (DI), a syndrome of inadequate release of or response to ADH 4. GI losses 5. Cathartic-containing Activate charcoal administration = pulls lyte-free H2O from ECS to GIT
64
Diabetes insipidus
DI pts depend on oral water intake to maintain normal plasma [Na+] because they cannot adequately reabsorb free water in the renal collecting duct -- become severely hypernatremic when they do not drink and hold down water
65
Cause for hyperNa+ : Water deficit – inadequate water intake | #2
1. hypernatremic if denied access to water for extended periods 2. syndrome of hypodipsic hypernatremia has been reported in Miniature Schnauzers → due to impaired osmoreceptor or thirst center function.
66
Cause for hyperNa+ : Increased sodium intake or retention | #4
Severe hypernatremia introduction of large quantities of sodium 1. hypertonic fluid administration (hypertonic saline, sodium bicarbonate) 2. sodium phosphate enemas 3. ingestion of seawater, beef jerky, or salt-flour dough mixtures. 4. Hyperaldosteronism can also cause hypernatremia due to excessive renal sodium retention
67
Clinical signs of hypernatremia
severe (usually >170 mEq/L) or occurs rapidly, -- -- Neurons intolerant of the cell volume change -- CNS signs such as obtundation, head pressing, seizures, coma, and death are the signs most commonly associated with clinical hypernatremia. ## Footnote Slow hyperNa+ typically asymptomatic
68
Physiologic adaptation to hypernatremia
cells w/ Na+/K+-ATPase pumps lose volume (shrink) from hyperNa+ → water moves freely through the water-permeable cell membrane while these plentiful electrolytes do not --causes free water to move out of the relatively hypOosmolar ICS into hyperosmolar ECS = **decreased cell volume**. -- **brain has adaptive ways to protect against neuronal water loss**
69
Cerebral protective mechanisms from HyperNa+
-- neuronal water is lost to the hyperNa+ circulation, ↓ interstitial hydrostatic pressure draws fluid from CSF into the brain interstitium -- As plasma osmolality rises, Na+ and Cl- move rapidly from CSF into cerebral tissue → helps minimize brain volume loss by ↑ neuronal osmolality = drawing water back into the cells -- w/i 24hr, neurons begin to accumulate organic solutes to ↑ intracellular osmolality and help shift lost water back into the cell
70
Organic solutes/Idiogenic osmoles aka osmolytes
molecules such as inositol and glutamate -- Generation and retention of these idiogenic osmoles begin within a few hours of neuron volume loss, though full compensation may take as long as 2–7 days
71
Normovolemia and HyperNa+
Hypernatremia should be treated even w/ no CS -- minor changes in [Na+] have been associated with poor outcome in people -- Patients with hyperNa+ have a water deficit = water should be replaced using fluid with a lower effective osmolality than the patient’s. -- [Na+] can be decreased by 0.5–1 mEq/L/hr in most situations of chronic or subacute hypernatremia without complication
72
Water supplementation | IV vs orally
Water may be supplemented intravenously (as 5% dextrose in water) or orally on an hourly schedule in animals that are alert, willing to drink, and not vomiting. ## Footnote Free water deficit calculation
73
When clinical signs of hypernatremia are present
water replacement must be more rapid Recent recommendation in people is to drop [Na+] in such cases by 2 mEq/L/hr until the [Na+] is high-normal
74
Treatment of acute sodium intoxication
-- some authors recommend rapid infusion of 5% dextrose in water paired with hemodialysis to restore normal [Na+] as calculated using the water deficit equation -- When hemodialysis is not possible, aggressive water replacement over ≤12 hours seems reasonable
75
Free water replacement with Cardiac or Kidney Dz
relatively safe, even in animals with cardiac or kidney disease, because the two-thirds of the infused volume that enters the cells cannot cause “fluid overload” or edema
76
Hyponatremia | #4
CS 2nd, uncommon in critically ill dogs and cats because signs are not usually seen unless [Na+] is very low, usually <120 mEq/L -- Causes: 1. Decreased effective circulating volume 2. Hypoadrenocorticism 3. Renal tubular dysfunction: Diuretics, kidney failure 4. Syndrome of inappropriate antidiuretic hormone secretion
77
Causes of HypoNa+: Decreased effective circulating volume
-- leads to ADH release and water intake in defense of intravascular volume = decreases [Na+]. -- CHF, Body cavity effusions, Edematous states → RAAS activation with increase water retention -- GI or Urinary Loss → compensatory drinking and retention
78
Causes of HypoNa+: Hypoadrenocorticism
-- leads to hypoNa+ via decreased sodium retention (caused by hypoaldosteronism) combined with increased water drinking and retention in defense of inadequate circulating volume -- low circulating cortisol concentration leads to increased ADH release and resultant water retention regardless of intravascular volume status -- Animals w/ atypical hypoadrenocorticism, whose aldosterone production and release are normal, may also develop hyponatremia.
79
Causes of HypoNa+: Renal tubular dysfunction: Diuretics, kidney failure
Loop or thiazide diuretic use causes hyponatremia by induction of hypovolemia, hypokalemia causing Na+ ions to shift **INTO** cells in **exchange** for K+ ions, and the inability to create dilute urine -- Kidney failure can cause hyponatremia by similar mechanisms.
80
Causes of HypoNa+: Syndrome of inappropriate antidiuretic hormone (ADH) secretion
Syndrome of inappropriate ADH secretion causes hyponatremia through water retention in response to improperly high circulating concentrations of ADH
81
Clinical signs of hyponatremia
cells w/ Na+/K+-ATPase pumps swell from hyponatremia b/c water moves into the relatively hyperosmolar cell from the hypoosmolar ECS -- **CNS signs consistent with cerebral edema**, such as obtundation, head pressing, seizures, coma, and ultimately death from brain herniation.
82
Physiologic adaptation to hyponatremia
Interstitial and intracellular CNS edema increases intracranial tissue hydrostatic pressure -- pressure enhances fluid movement out of neurons and into the CSF, which flows out of the cranium, through the subarachnoid space and central canal of the spinal cord, and back into venous circulation -- Swollen neurons also expel solutes such as Na+/K+ and organic osmolytes to decrease intracellular osmolality and encourage water loss to the ECF, returning cell volume toward normal.
83
osmotic demyelination syndrome (ODS), or myelinolysis
Complications of **HypoNa+ treatment** -- ODS is the result of **neuronal shrinking away from the myelin sheath as water moves out of the neuron during correction of hyponatremia.** -- myelinolysis commonly seen in thalamus -- CS usually manifest days after intervention, so the clinician cannot assume that a rapid change in plasma [Na+] has been well tolerated simply because no CNS signs are present during initial treatment. ## Footnote limb paresis, dysphagia, ataxia, and disorientation
84
Rapid correction of HypONa+ can lead to:
Overzealous correction of severe hyponatremia has led to paresis, ataxia, dysphagia, obtundation, and other neurologic signs in dogs
85
Treating asymptomatic hyponatremia
-- hyponatremia caused by decreased effective circulating volume usually evolves over time -- Hyponatremia due to poor effective circulating volume usually self-corrects with improvement in perfusion, as ADH secretion drops and water is eliminated by the kidney -- Asymptomatic patients that are edematous may be treated with water restriction alone, and those that are asymptomatic and normally hydrated or dehydrated may be treated with administration of fluids with a sodium concentration that exceeds the patient’s [Na+].
86
Correction rate for hypoNa+
chronic or the evolutionary timeline is unknown, the goal is to raise patient [Na+] by no more than **10 mEq/L during the first 24 hours** and by **no more than 8 mEq/L during each following 24-hour period,** not to exceed the low end of the reference interval some authors recommend an increase of **no more than 8 mEq/L over any 24-hour period,** particularly if risk for ODS is high due to severity or chronicity of the hyponatremia.
87
Effect of HypoK+ supplementation with HypoNa+
when correcting hyponatremia in animals being treated for concurrent hypokalemia → potassium supplementation will speed the correction of hyponatremia.
88
Cerebral Edema from severe acute HypoNa+
rapid water influx into neurons may exceed these cells’ ability to expel solute and water quickly enough -- Cerebral edema is treated with 7.0%–7.5% sodium chloride (hypertonic saline) at 3 to 5 ml/kg over 20 minutes.
89
Pseudohyponatremia
hyponatremia in a patient with normal or elevated plasma osmolality -- most common cause in dogs and cats is hyperglycemia -- when **hyperglycemia is present, the excess glucose molecules cause an increase in ECF water, diluting sodium to a lower concentration.** -- other common cause is **mannitol infusion with retention (rather than renal excretion) of mannitol molecules**
90
Hyperglycemia relationship to Sodium level
For each 100 mg/dl increase in blood glucose, [Na+] drops by approximately 1.6–2.4 mEq/L.
91
% of K+ located intracellular
99%
92
Where do majority of intracellular K+ reside?
Skeletal muscle cells
93
Average potassium concentration
K+ concentration in intracellular space of dogs and cats is 140 mEq/L -- plasma space averages 4 mEq/L. -- Serum potassium levels therefore do not reflect whole body content or tissue concentrations.
94
Body’s potassium regulation | #5
pH regulation changes in osmolality insulin catecholamines aldosterone
95
Solvent drag
Hyperosmolality causes the translocation of water from the cellular space, which drags cellular potassium into the extracellular fluid space
96
Hormone effects on K+ ## Footnote x3
Insulin, catecholamines, and aldosterone transfer potassium from the extracellular space to the intracellular space.
97
Aldosterone effect on K+
Any increase in extracellular fluid potassium concentration triggers aldosterone release, which acts at the** distal renal tubules to increase Na-K-ATPase activity** -- promotes the transluminal transfer of potassium ions through the collecting duct principal cells into the renal tubular lumen, thus **allowing for potassium excretion and sodium reabsorption.**
98
Kaliuretic feedforward control | Where are the sensors? What effects does it cause?
responds to signals in the external environment and involves **sensors in the stomach and the hepatic portal regions** -- sensors detect local changes in potassium concentrations resulting from potassium ingestion and signal the kidney to alter potassium excretion to restore potassium balance -- **done without the influence of aldosterone.**
99
Hypokalemia: causes
**(1) disorders of internal balance** Metabolic alkalosis Insulin administration Increased levels of catecholamines β-Adrenergic agonist therapy or intoxication Refeeding syndrome **(2) disorders of external balance** Renal potassium wasting Prolonged inadequate intake Diuretic drugs Osmotic or postobstructive diuresis Chronic liver disease Inadequate parenteral fluid supplementation Aldosterone-secreting tumor or any cause of hyperaldosteronism Prolonged vomiting associated with pyloric outflow obstruction Diabetic ketoacidosis Renal tubular acidosis Severe diarrhea Ingestion of barium-containing party sparklers glucocorticoid drugs Glucocorticoid drug administration
100
Neuromuscular effects of HypoK+
K+ necessary for **maintenance of normal resting membrane potential** -- neuromuscular abnormality induced by hypokalemia in dogs and cats is **skeletal muscle weakness from hyperpolarized (less excitable) myocyte plasma membranes** that may progress to hypopolarized membranes. -- ventroflexion or head neck, stiff gait, plantagrade stance
101
HypoK+ effect on myocardial cells
high intracellular/extracellular potassium concentration ratio induces a state of electrical hyperpolarization leading to prolongation of the action potential -- predisposes patient to atrial and ventricular tachyarrhythmias, atrioventricular dissociation, and ventricular fibrillation
102
HypOK+ EKG findings
Canine ECG abnormalities include **depression of the ST segment and prolongation of the QT interval** -- Increased P wave amplitude, prolongation of the PR interval, and widening of the QRS complex may also occur -- predisposes to digitalis-induced cardiac arrhythmias -- causes the **myocardium to become refractory to the effects of class I antiarrhythmic agents** (i.e., lidocaine, quinidine, and procainamide).
103
Causes of Hyperkalemia: Increased intake or supplementation | #10
1. Intravenous potassium-containing fluids 1. Expired RBC transfusion 1. Drugs (potassium penicillin G, KCl, KPhos) 1. Translocation from ICF to ECF 1. Mineral acidosis (respiratory acidosis, NH4Cl, HCl, uremia) 1. Insulin deficiency 1. Acute tumor lysis syndrome 1. Extremity reperfusion following therapy for thromboembolism 1. Drugs (nonspecific β-blockers, cardiac glycosides) 1. Cardiopulmonary arrest
104
Causes of Hyperkalemia: Decreased urinary excretion | #12
1. Anuric or oliguric renal injury 1. Urethral obstruction, bilateral ureteral obstruction 1. Uroabdomen 1. Hypoadrenocorticism 1. Gastrointestinal disease (trichuriasis, salmonellosis, perforated duodenum) 1. Chylothorax or pleural or peritoneal effusions 1. Drugs (ACE inhibitors, angiotensin receptor blockers, heparin, cyclosporine and tacrolimus, non-steroidal anti- inflammatory drugs, trimethoprim) 1. Pseudohyperkalemia 1. Thrombocytosis or leukocytosis (>1,000,000 platelets or >100,000 leukocytes) 1. Akita dog and other dogs of Japanese origin (secondary to in-vitro hemolysis) 1. Idiopathic 1. General anesthesia in healthy dogs (most notably Greyhounds)
105
HyperK+ with Mineral Acidosis
-respiratory acidosis, uremia or pharmacologic induction by ammonium chloride, hydrogen chloride, or calcium chloride infusions -- causing potassium to move out of the intracellular space in exchange for hydrogen ions.
106
HyperK+ with Diabetes | #3
* insulin deficiency that results in a decreased cellular uptake of potassium * hyperosmolality that potentiates potassium translocation with water due to “solute drag” effect * decreased potassium excretion related to renal dysfunction (comorbidities, a prerenal component, or an acute kidney injury relative to hypovolemia/perfusion).
107
EKG changes with HyperK+ | #6
1. peaked, narrow T waves 1. prolonged QRS complex and interval 1. depressed ST segment 1. depressed P wave 1. atrial standstill 1. ventricular flutter/fibrillation
108
HyperK+ from Renal Dz ## Footnote what is it dependent on? where does this take place in the kidney?
-- distal tubule is dependent on both adequate **glomerular filtration rate and urine flow to excrete potassium** -- severe reduction in both of these determinants with acute kidney injury significantly **impairs the ability of the distal tubule to excrete sufficient potassium**
109
HyperK+ from hypoadrenocorticism
In the absence of aldosterone, the resulting natriuresis causes a reduced effective circulating volume, which further impairs distal tubule potassium excretion.
110
Pseudohyperkalemia
Potassium can be released from increased numbers of circulating blood cells, especially platelets and leukocytes, causing an artifactual increase in potassium -- Akitas/japanese dogs
111
Consequences of HyperK+ | #3 ## Footnote how does it affect cardiac myocytes?
causes changes in **cardiac myocyte excitation and conduction** -- the concentration gradient across the cardiac cell membranes is reduced, **leading to a less negative resting membrane potential = makes cardiac cell membranes more excitable.** -- inactivates some of the Na+/K+ channels during the resting phase, making **these cells slower to reach threshold potential** -- **Acidemia results in extracellular shift in potassium as well as decreasing the β-adrenergic** receptors in cardiac tissues.
112
HyperK+ treatment: Ca++ Gluconate
-- antagonize cardiotoxic effects of hyperK+ -- Increases threshold voltage but will not lower serum potassium
113
HyperK+ treatment: HCO3-
Causes metabolic alkalosis allowing for potassium to move intracellularly, paradoxical CNS acidosis with rapid administration
114
HyperK+ treatment: 50% Dextrose
Allows for translocation of potassium into the intracellular space in the presence of endogenous insulin
115
HyperK+ treatment: Terbutaline
Stimulates Na+/K+-ATPase to cause translocation of potassium into the cell
116
Calcium homeostasis
necessary for muscle contraction, neuromuscular function, and skeletal bone support
117
Three forms of circulating calcium exist in serum and plasma:
1. ionized (free), 1. protein bound 1. complexed (calcium bound to phosphate, bicarbonate, lactate, citrate, oxalate) Total calcium measures all 3
118
Ionized Ca++
biologically active form in the body and is considered the most important indicator of functional calcium levels
119
Calcium regulation ## Footnote where does it occur? what organs are involved?
complex process involving primarily parathyroid hormone (PTH), vitamin D metabolites, and calcitonin -- most of their effects seen on the intestine, kidney, and bone
120
primarily parathyroid hormone (PTH) what inhibits/stimulates it? | what is it secreted by?
synthesized and **secreted by the chief cells** of the parathyroid gland in response to hypocalcemia --normally inhibited by increased serum ionized calcium levels, as well as by increased concentrations of circulating calcitriol
121
How does PTH increase Ca++ levels? | #3
through increased tubular reabsorption of calcium increased osteoclastic bone resorption increased production of calcitriol that then increases intestinal absorption of calcium
122
Vitamin D and its metabolites
-- Cats and Dogs depend on Vit D in their diet -- cannot photosynthesize Vit D efficiently from their skin (like humans) -- After ingestion and uptake, vitamin D (**cholecalciferol**) is first hydroxylated in the liver and then it is **further hydroxylated to calcitriol** by the proximal tubular cells of the kidney -- **final hydroxylation** by the 1α-hydroxylase enzyme system to form **active calcitriol**
123
Calcitriol Synthesis | What effects its levels? where does it act primarily?
* Decreased levels of phosphorus, calcitriol, and calcium promote calcitriol synthesis * Increased levels of these substances all cause a decrease in calcitriol synthesis. * calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland
124
Calcitriol MOA in instestine
In the intestine, calcitriol enhances the absorption of calcium and phosphate at the level of the enterocyte
125
Calcitriol MOA in bones
-- promotes bone formation and mineralization by regulation of proteins produced by osteoblasts -- also necessary for normal bone resorption because of its effect on osteoclast differentiation
126
Calcitriol effects on Kidneys
calcitriol acts to inhibit the 1α-hydroxylase enzyme system, as well as **promote calcium and phosphorus reabsorption** from the glomerular filtrate
127
Calcitriol effects on parathyroid
calcitriol acts genomically to inhibit the synthesis of PTH
128
HARDIONS G | Hypercalcium differentials
**H**yperparathyroidism **A**ddison’s disease **R**enal failure Vitamin **D** toxicosis e.g. from rodenticides, house plants or psoriasis creams **I**diopathic (this is mainly a feline condition) **O**steolytic e.g. osteomyelitis **N**eoplasia e.g. lymphoma, anal sac adenocarcinoma **S**purious i.e. rule out lab error before starting investigation **G**ranulomatous disease ## Footnote diagnosis of hypercalcemia is confirmed with an ionized calcium measurement generally greater than 6 mg/dl or 1.5 mmol/L in the dog or greater than 5.7 mg/dl or 1.4 mmol/L in the cat.
129
CS of HyperCa++
-- polyuria and polydipsia (uncommon in cats), anorexia, constipation, lethargy, and weakness -- Severely affected animals may display ataxia, obtundation, listlessness, muscle twitching, seizures, or coma -- EKG abnormalities
130
EKG abnormalities with HyperCa++
**Bradycardia** may be detected on physical examination -- **prolonged PR interval**, widened QRS complex, shortened QT interval, shortened or absent ST segment, and a widened T wave.
131
neoplasia-associated hypercalcemia
specifically lymphoma, the most common cause in dogs
132
Type of Rat poison causing HyperCa++
Rat bait containing cholecalciferol
133
HyperCa++ Crisis
134
HyperCa++ Treatment
Definitive treatment for hypercalcemia involves removing the underlying cause -- Acute therapy often involves the use of one or more of the following: intravenous fluids, diuretics (furosemide), glucocorticoids, and calcitonin
135
therapeutic fluid of choice for HyperCa++
0.9% sodium chloride -- additional sodium ions provide competition for renal tubular calcium reabsorption, resulting in enhanced calciuria -- In addition, 0.9% sodium chloride is calcium-free, unlike other isotonic crystalloids
136
How does HyperCa++ cause hypertension?
hypercalcemia can contribute to the development of hypertension secondary to vasoconstriction
137
Furosemide's affect on Ca++
enhances urinary calcium loss -- calciuresis
138
Glucocorticoid affects on Ca++ | #3
can cause a reduction in serum calcium concentration -- reduced bone resorption -- decreased intestinal calcium absorption -- increased renal calcium excretion
139
Calcitonin effects for HyperCa++ tx
Calcitonin acts to decrease serum calcium concentrations mostly by **reducing the activity and formation of osteoclasts**
140
HCO3- effects for HperCa++ tx
decreases the ionized and total calcium
141
Bisphosphonates for HyperCa++ tx
**decrease osteoclastic activity**, thus **decreasing bone resorption** -- not considered drugs of choice for acute or crisis therapy -- can cause esophageal irritation and have been reported to cause abdominal discomfort, nausea, and vomiting in humans -- Bone toxicity from long-term treatment with bisphosphonates has been reported ## Footnote Pamidronate, zoledronate
142
Hypocalcemia ## Footnote x3 causes
Decreased total serum calcium is particularly common in those with **low circulating albumin status** -- common for **cats with pancreatitis** to have ionized hypocalcemia -- **Eclampsia in dogs**
143
Clinical Signs Associated with Hypocalcemia | List as many you can think of
1. Muscle tremors or fasciculations 1. Facial rubbing 1. Muscle cramping 1. Stiff gait 1. Behavioral change 1. Restlessness or excitation 1. Aggression 1. Hypersensitivity to stimuli 1. Disorientation 2. seizures 1. Panting 1. Pyrexia 1. Lethargy 1. Anorexia 1. Prolapse of third eyelid (cats) 1. Posterior lenticular cataracts 1. Tachycardia or ECG alterations (i.e., prolonged QT interval) **Uncommon:** 1. Polyuria or polydipsia 1. Hypotension 1. Respiratory arrest or death
144
Differential Diagnoses for Hypocalcemia ## Footnote x8
Hypoalbuminemia Chronic renal failure Eclampsia Acute kidney injury Pancreatitis Soft tissue trauma or rhabdomyolysis Hypoparathyroidism Intestinal malabsorption, PLE, starvation ## Footnote theres like so many
145
HypoCa++ tx
-- **HyperMg++ and hypOMg++ can impair the secretion of PTH** and PTH actions on its receptor, so measurement of serum magnesium (preferably ionized magnesium) is important, especially in animals with **refractory hypocalcemia** -- treat the primary disease causing the disorder -- typically involves the administration of calcium salts, as well as vitamin D metabolites
146
possible complications of ionized hypocalcemia
severe ionized hypocalcemia can be life threatening because of myocardial failure and respiratory arrest tachycardia ECG alterations (i.e., prolonged QT interval) refractory hypotension respiratory arrest
147
Serum Mg++
less than 1% of total body magnesium is in the serum, serum magnesium concentrations do not always reflect total body magnesium stores -- normal serum magnesium concentration can occur when there is a total body magnesium deficiency. -- ionized, anion-complexed, and protein-bound fractions.
148
Where does Mg++ reside in the body?
-- **second most abundant intracellular cation**, exceeded only by potassium Most of the magnesium is **found in bone and muscle.** **60%** of total body magnesium content is **present in bone.** **20% is in skeletal muscle** remainder is in other tissues, primarily the heart and liver
149
Mg++ Bodily uses | #5
1. required for many metabolic functions 1. production and use of ATP 1. essential for protein and nucleic acid synthesis 1. regulation of vascular **smooth muscle tone** cellular second messenger systems 1. signal transduction
150
Magnesium homeostasis
achieved through **intestinal absorption and renal excretion** -- Absorption occurs primarily in the small intestine **(jejunum and ileum)**
151
Renal managment of Mg++
**LOH and DCT** are the main sites of magnesium reabsorption in the kidney -- **kidney is the main regulator** of serum magnesium concentration and total body magnesium content regulation is achieved by both glomerular filtration and tubular reabsorption
152
Lactation effects on Mg++
Increased concentrations of PTH, in addition to calcium concentration, most likely participate in magnesium conservation during lactation to supply the mammary glands with a sufficient amount
153
Hypomagnesemia Causes | #6
1. Decreased Intake 2. perioperative feline renal transplant recipients cats with diabetes mellitus and diabetic ketoacidosis 1. receiving peritoneal dialysis 2. dogs with congestive heart failure receiving furosemide therapy 1. protein-losing enteropathy 1. lactating dogs ## Footnote Magnesium losses can occur through the GI tract, kidneys, or both.
154
HypoMg++: Increased Losses
GIT: i**nflammatory bowel disease, malabsorptive or short-bowel syndromes, or other diseases that cause prolonged diarrhea.**
155
HypoMg++: Renal
Acute renal dysfunction as a consequence of glomerulonephritis or the nonoliguric phase of acute tubular necrosis is often associated with a rise in the fractional excretion of magnesium
156
HypoMg++: Drugs
diuretic agents (furosemide, thiazides, mannitol) induce hypomagnesemia by increasing urinary excretion -- aminoglycosides, amphotericin B, cisplatin, and cyclosporine
157
Clinical signs: HypoMg++
changes in resting membrane potential, signal transduction, and smooth muscle tone -- effects of magnesium on the myocardium are linked to its role as a **regulator of other electrolytes, primarily calcium and potassium** -- cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation
158
EKG abnormalities from HypoMg++
-- **prolongs conduction through the atrioventricular node** -- prolongation of the PR interval, widening of the QRS complex, depression of the ST segment, and peaking of the T wave
159
Neuromuscular effects of HypoMg++
**increases acetylcholine release from nerve terminals and enhances the excitability of nerve and muscle membranes** -- **increases the intracellular calcium content** in skeletal muscle -- **generalized muscle weakness, muscle fasciculations, ataxia, and seizures** -- **Esophageal or respiratory muscle weakness** can be manifested as dysphagia or dyspnea
160
Refractory HypoK+
hypokalemia that is refractory to aggressive potassium supplementation **may be due to magnesium deficiency causing excessive potassium loss through the kidneys**
161
HypoCa++ from HypoMg++
**hypomagnesemia impairs PTH release and enhances calcium movement from extracellular fluid to bone** -- total and ionized hypocalcemia often accompanies magnesium depletion -- clinical signs of hypocalcemia seen with hypoMg++ possible
162
HypoMg++ tx
**Parenteral administration of magnesium sulfate may result in hypocalcemia because of chelation of calcium with sulfate** = magnesium chloride should be given if hypocalcemia is also present
163
Side effects of Mg++ supplementation
-- hypotension, atrioventricular block, and bundle branch blocks -- usually are associated with intravenous boluses rather than CRIs
164
HyperMg++ causes | #3
renal failure/kidney injury, endocrinopathies, and iatrogenic overdose, especially in patients with impaired renal function -- degree of hypermagnesemia parallels the degree of renal failure
165
Clinical signs HyperMg++
-- lethargy, depression, and weakness -- Other clinical signs reflect the electrolyte’s action on the nervous and cardiovascular systems -- hyporeflexia = **decreased skeletal muscle response** -- **respiratory depression secondary to respiratory muscle paralysis in w/ profound elevation** -- **blockade of the autonomic nervous system**
166
EKG abnormalities with HyperMg++
-- prolongation of the PR interval and widening of the QRS complex due to delayed atrioventricular and interventricular conduction. -- Bradycardia -- severely high serum magnesium concentrations, complete heart block and asystole can occur
167
HyperMg++ tx
-- **Saline diuresis and furosemide** can also be used to accelerate renal magnesium excretion -- severe cases involving unresponsiveness **treated with intravenous calcium** -- **Calcium is a direct antagonist of magnesium at the neuromuscular junction** and may be beneficial in reversing the CVS effects of hypermagnesemia -- **anticholinesterase treatment** may be administered to offset the neurotoxic effects (Physostigmine)
168
Phosphorus Homeostasis | soo manyyy
-- body’s **major intracellular anion** -- essential for the production of ATP, guanosine triphosphate, cyclic adenosine monophosphate, and phosphocreatine, all of which function to **maintain cellular membrane integrity, energy** stores, metabolic processes, and biochemical messenger systems -- maintenance of **normal bone and teeth matrix** in the form of hydroxyapatite -- regulation of **tissue oxygenation** by way of 2,3-di-phosphoglycerate (**2,3-DPG**) -- support of cellular membrane structure -- buffering acidotic conditions
169
Distribution of Phosphorus in the body | Organic vs Inorganic
* 80% to 85% in the bone and teeth as inorganic hydroxyapatite * 14% to 15% in soft tissues * less than 1% in the extracellular space -- Phosphorus is present in the body as organic and inorganic phosphates -- **Organic phosphate is mostly intracellular** and **inorganic phosphate is mostly extracellular.**
170
Inorganic phosphate
Inorganic phosphate in the **form of 2,3-DPG accounts for 70% to 80% of phosphate in RBCs** -- Inorganic phosphate is further divided into orthophosphates and pyrophosphates -- most extracellular inorganic phosphate is in the form of orthophosphates
171
Organic Phosphate
components of phospholipids, phosphoproteins, nucleic acids, enzymes, cofactors -- two-thirds of organic phosphate is in the form of phospholipids
172
Which type of phosphate do blood chemical analyzers measure?
blood chemistry analyzers only measure the **inorganic phosphates**
173
Phosphate regulation
60% to 70% of ingested phosphate is **absorbed in small intestine** -- Serum phosphate balance is **dependent on GFR and tubular reabsorption in PCT** -- amount of phosphate reabsorbed is **dependent on dietary intake**
174
Effects of hormones on Phosphorus
-- **(PTH) is a phosphaturic hormone** because it **decreases the tubular transport maximum for phosphate reabsorption** -- **Growth hormone, insulin**, insulin-like growth factor 1, and **thyroxine increase tubular phosphate reabsorption** -- **Growth hormone partially accounts for the expected hyperphosphatemia in young, growing animals**
175
Body's phosphate reservior
**skeleton is the body’s phosphate reservoir** and provides a readily available source of phosphate **during periods of hypophosphatemia under the regulation of PTH and calcitonin**
176
HypoPhos- Causes | #4
1. Decreased Gastrointestinal Absorption 1. Transcellular Shifts 1. Increased Urinary Loss 1. Spurious or Laboratory Error
177
Transcellular Shifts of Phos- | #7
associated with: 1. alkalemia, 1. hyperventilation, 1. refeeding syndrome, 1. parenteral nutrition, 1. insulin administration, 1. glucose administration, 1. catecholamine administration or release, and salicylate toxicity
178
Refeeding syndrome effects on Phos-
**Hypophosphatemia** is the **most common and critical electrolyte disturbance associated with refeeding syndrome. ** During chronic malnutrition, phosphate depletion can occur and may not be reflected by a decrease in serum phosphate concentration. Administration of enteral or parental nutrition to a patient with chronic malnutrition **stimulates insulin release, which promotes intracellular uptake of phosphate and glucose for glycolysis;** -- this transcellular shift may result in severe hypophosphatemia.
179
Insulin and Glucose effects on Phos-
-- Insulin and glucose administration can cause severe hypophosphatemia in a patient with total body phosphate depletion -- stimulate glycolysis, promoting the synthesis of phosphorylated glucose compounds and intracellular shifts of phosphate.
180
Cellular effects of HypoPhos-
severe hypophosphatemia and total body phosphate depletion **can result in widespread cellular dysfunction** -- **Hemolysis** can occur with severe hypophosphatemia because of decreased concentrations of red blood cell ATP and 2,3-DPG, spherocytosis -- **Decreased intracellular 2,3-DPG** = **impairs release of oxygen by hemoglobin to tissues**, = **tissue hypoxia** -- chemotaxis, phagocytosis, and bactericidal activity of leukocytes, which increases the risk of infection in critically ill animals ## Footnote O2/Hb CURVE
181
CS of HypoPhos-
-- skeletal muscle changes include generalized weakness, tremors, and muscle pain -- Rhabdomyolysis (breakdown of muscle tissue) secondary to acute hypophosphatemia from refreeding syndrome -- **Neurologic signs** may include ataxia, seizures, and coma associated with **metabolic encephalopathy**
182
HyperPhos- causes
decreased renal excretion increased intake iatrogenic administration, and transcellular shifts -- decreased excretion are AKI, acute-on-chronic kidney disease, urethral obstruction, and uroabdomen
183
HyperPhos- from transcellular shifts of phosphate
-- occur with **tumor lysis syndrome, rhabdomyolysis, and hemolysis** -- Tumor lysis syndrome is the clinical manifestation and laboratory sequelae of acute death of tumor cells that release potassium, phosphate, and nucleic acids into circulation and may cause AKI
184
Rhabdomyolysis causing HyperPhos-
syndrome of massive skeletal muscle tissue injury -- can cause hyperphosphatemia directly from **release of intracellular contents and indirectly by decreased renal excretion** from **resulting myoglobin-induced AKI** (although is rare in cats or dogs).
185
Iatrogenic overdose of Phosphorus
large doses of parenteral phosphate can cause not only hyperphosphatemia but **also hypomagnesemia, hypocalcemia, and hypotension** -- **Ingestion of cholecalciferol rodenticides and vitamin D3** skin creams (e.g., calcipotriene) can **rapidly increase serum phosphate concentration by increased intestinal absorption and release from bones**
186
CS of HyperPhos-
**anorexia, nausea, vomiting, weakness, tetany, seizures, and dysrhythmias** -- Clinical manifestations of hyperphosphatemia **predominantly are due to hypocalcemia and ectopic soft tissue calcification**
187
Soft tissue effects from HyperPhos-
Soft tissue calcium phosphate accumulation occurs when the calcium phosphate product is greater than 58 to 70 mg2/dl2 -- Tissues primarily affected by ectopic calcification include **cardiac, vasculature, renal tubules, pulmonary, articular, periarticular**, conjunctival, skeletal muscle, and skin
188
EKG abnormalities from HyperPhos-
Arrhythmias: **polymorphic ventricular tachycardia or torsades de pointes** caused by prolongation of the QT interval, are **also associated with subsequent hypocalcemia and hypomagnesemia**
189
pH relationship with HCO3- and CO2
pH has a direct relationship with bicarbonate concentration and an inverse relationship with PCO2
190
three major processes for acid-base balance:
1. regulation of PCO2 by alveolar ventilation (respiratory component) 1. buffering of acids by bicarbonate nonbicarbonate buffer systems (metabolic component) 1. changes in renal excretion of acid or base
191
Henderson-Hasselbalch equation
uses pH, PCO2 and bicarbonate concentration for carbonic acid (H2CO3) -- pH is the consequence of the ratio of bicarbonate to PCO2.
192
PCO2
Carbon dioxide acts as an acid in the body because of its ability to react with water to produce carbonic acid (H2CO3) -- increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls.
193
carbonic acid equation
CO2 + H2o ←→ H2CO3 ←→ H+ + HCO3- ## Footnote * increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls. * with an increase in PCO2, the carbonic acid equation (below) will be driven to the right, increasing the hydrogen ion concentration
194
Bicarbonate
-- Elevations in bicarbonate concentration will drive the pH higher and represent a metabolic alkalosis while decreases in bicarbonate concentration represent a metabolic acidosis -- elevations in PCO2 will lead to elevations in bicarbonate while decreases in PCO2 will lead to a decrease in bicarbonate
195
Base excess Increased vs Decreased amount | Definition
defined as the **amount of strong acid or strong base** (in mmol/L) that **must be added** to 1 liter of fully oxygenated whole blood **to restore the pH to 7.4 ** -- **increased BE** (more positive value) is **consistent with a metabolic alkalosis** (either gain of bicarbonate or loss of acid) -- **decreased BE** (more negative value) **represents a metabolic acidosis**
196
Base Excess relationship with PCO2
-- advantage of using BE over bicarbonate concentration is that it is **independent of changes in the respiratory system** -- minimal changes in PCO2 present, the **BE and bicarbonate should correlate well** -- with substantial abnormalities in PCO2, the **BE is a more reliable measure of the metabolic component**
197
Total carbon dioxide | what does it represent?
-- represents the metabolic acid-base component, not the respiratory system component -- measure of all the CO2 in a blood sample, and the majority of CO2 is carried as bicarbonate in the blood
198
Anion gap definition
-- Electroneutrality requires there to be an equal number of anions and cations in a physiologic system -- In reality there is no actual AG; the apparent AG exists because more cations in the system are readily measured than anions -- reflection of unmeasured ions
199
Metabolic Acidosis: 1st mechanism
-- Bicarbonate concentration can fall with a rise in chloride concentration = **hyperchloremic metabolic acidosis** -- due to **disease processes causing bicarbonate loss in the gastrointestinal tract, or kidneys or can be iatrogenic,** secondary to administration of sodium chloride
200
Metabolic Acidosis: 2nd mechanism
occur from the **gain of acid** → excess acid in the system, **hydrogen ions will titrate (combine) with bicarbonate, leading to a fall in bicarbonate concentration** -- anion that accompanies the hydrogen ion (the conjugate base) will accumulate, maintaining electroneutrality and increasing the AG
201
HAGMA
High Anion Gap Metabolic Acidosis -- common causes of increased AG metabolic acidosis in small animals is DUEL -- AG can be calculated in an effort to help determine the underlying cause of the abnormality, assuming the patient is not hypoalbuminemic
202
DUEL causes for HAGMA
**D**iabetic ketoacidosis **U**remic acids **E**thylene glycol toxicity **L**actic acidosis
203
Hyperchloremic Metabolic Acidosis causes
* Renal bicarbonate loss * Gastrointestinal bicarbonate loss * Sodium chloride administration * Hypoadrenocorticism
204
Normal unmeasured anions
Albumin and phosphorus -- states of hypoalbuminemia, abnormal unmeasured anions (e.g., **lactate or ketones**) may be present, but the calculated AG may remain within the reported normal range -- **AG is not reliable in hypoalbuminemic patients** -- Conversely, hyperalbuminemia will increase AG
205
Mixed Acid-Base disorder
-- abnormality in both the metabolic and respiratory components -- evident when both the respiratory and metabolic components have the same influence on acid-base balance (i.e., metabolic acidosis and respiratory acidosis or metabolic alkalosis and respiratory alkalosis) -- also present when there are abnormalities evident in both the metabolic and respiratory components, but the pH is in the normal range
206
Respiratory acidosis
-- results from an imbalance in CO2 production via metabolism and CO2 excretion via alveolar minute ventilation of the lung -- consequence of increased CO2 production or decreased alveolar ventilation -- diseases that **reduce respiratory rate, tidal volume, or both** -- Diseases that **prevent the transmission of impulses from the respiratory center to the respiratory muscles,** such as **cervical spinal cord disease, peripheral neuropathies** and diseases of the neuromuscular junction, can all cause respiratory paralysis and respiratory acidosis -- severe cases require MV
207
Respiratory alkalosis | Dz process that cause Resp Alk
-- decreased PCO2 is the result of an increase in VA -- **disease processes that may stimulate an increased respiratory rate and/or tidal volume** -- include **significant hypoxemia, pulmonary parenchymal disease** (causing stimulation of **stretch receptors or nociceptors**), and airway inflammation -- central stimulation of respiratory rate and effort by the respiratory center → pathologic process resulting from brain injury, or it could be **behavioral as a result of pain or anxiety**.
208
What accurately determines Ventilatory status?
most accurately determined by measurement of PaCO2. -- PvCO2 can be used to evaluate ventilation **if the animal is cardiovascularly stable**
209
Metabolic acidosis
210
renal tubular acidosis (RTA) causes | Distal vs Proximal
Renal loss of bicarbonate from proximal or distal tubular dysfunction -- **proximal RTA,** there is **inadequate reabsorption of bicarbonate** in the proximal nephron -- **Distal RTA** is a disorder involving **inadequate hydrogen ion secretion** in the distal tubule that prevents maximal acidification of the urine pyelonephritis and IMHA | Fanconi syndrome - congenital dz ## Footnote Renal loss of bicarbonate can be an appropriate response to a persistent respiratory alkalosis (metabolic compensation)
211
Metabolic acidosis tx
-- Fluids containing a buffer such as lactated Ringer’s solution will aid in the metabolism of hydrogen ions -- hyperchloremic metabolic acidosis, use of lower chloride containing fluids (i.e., avoiding 0.9% NaCl) will also be of benefit. -- Treatment of metabolic acidosis due to an acid gain is primarily focused on the resolution of the underlying cause and appropriate selection of IV fluid therapy (DKA)
212
When would bicarb administration be warranted?
When the acidosis is severe or the compensatory respiratory alkalosis is considered detrimental to the patient, bicarbonate administration is indicated
213
Metabolic alkalosis
Metabolic alkalosis can broadly be considered to occur due to either acid loss or bicarbonate gain -- Causes of acid loss include selective gastric acid loss such as can occur with gastrointestinal obstructive processes, excessive nasogastric tube suctioning -- Renal acid loss can occur due to loop diuretic administration, mineralocorticoid excess, and the presence of nonresorbable anions such as carbenicillins
214
Cl- relationship with Metabolic Alkalosis
Acid loss invariably occurs along with chloride in the gastrointestinal tract and renal system, and as a result, many animals with metabolic alkalosis will also be hypochloremic
215
K+ relationship with Metabolic Alkalosis
Hypokalemia can play a significant role in the generation and maintenance of metabolic alkalosis. -- Intracellular shifts of hydrogen ions in exchange for potassium ions leaving the cells will increase the pH of the extracellular fluid. -- hypokalemia promotes renal acid loss -- **converse is true with acidemia**
216
K+/H+ exchange
-- cells exchange hydrogen ion for a potassium ion, using a special ion transporter located across the cell membrane. -- in order to help compensate for an acidosis, hydrogen ions enter cells and potassium ions leave the cells and enter the blood --In the acidotic patient there is a pseudo-hyperkalaemic state that may not reflect the total body potassium -- **Converse is true for alkalosis**
217
Renal production of Bicarb
kidney has the ability to excrete large quantities of bicarbonate, such that metabolic alkalosis should be rectified rapidly. When metabolic alkalosis is persistent, there must be factors limiting renal bicarbonate excretion
218
What process can affect Renal bicarb production? | #4
Decreased effective circulating volume hypochloremia can both limit renal bicarbonate excretion. Hypokalemia and aldosterone excess further impair renal bicarbonate excretion
219
Consequences of Metabolic Acidosis | #7
1. decreased myocardial contractility 1. arterial vasodilation 1. impaired coagulation 1. increased work of breathing secondary to carbon dioxide production 1. decreased renal and hepatic blood flow 1. insulin resistance 1. altered central nervous function
220
Bicarbonate therapy | when is it contraindicated?
bicarbonate binds hydrogen ions (hence the alkalinizing effect) to form carbonic acid → this rapidly dissociates to CO2 and water -- If ventilation does not increase appropriately, an elevated PCO2 will cause a decrease in pH -- contraindicated in patients with evidence of hypoventilation
221
Adverse effects of Bicarb therapy | #11
1. Increased hemoglobin affinity for oxygen 1. Increased blood lactate concentration 1. Paradoxical intracellular acidosis 1. Hypercapnia 1. Hypervolemia 1. Hyperosmolality 1. Hypernatremia 1. Hypocalcemia (ionized) 1. Hypomagnesemia (ionized) 1. Hypokalemia 1. Phlebitis
222
paradoxical intracellular acidosis
Bicarbonate cannot freely cross cell membranes, but the CO2 produced as bicarbonate is metabolized can freely enter cells -- Once intracellular, the CO2 combines with water leading to hydrogen ion release, causing intracellular acidosis -- evidence shows decreases in cellular and cerebrospinal fluid pH following bicarbonate therapy
223
strong ion difference approach | #3 components
1. partial pressure of carbon dioxide (PCO2) 1. the difference between strong cations and strong anions, known as the SID 1. total nonvolatile weak acids ## Footnote (sodium + potassium) − (chloride)
224
Strong ion difference | Definition Ions included
ions that are fully dissociated at physiologic pH -- major strong ions include sodium, potassium, calcium, magnesium, and chloride -- sodium and chloride are the most important strong ions in the body and SID is commonly simplified as the difference between serum sodium and chloride concentrations
225
Decreased SID metabolic acidosis ## Footnote Causes fluid tx choice
due to hyponatremia, hyperchloremia, or a combination of the two -- may be best treated with an IV fluid with a higher SID, such as lactated Ringer’s with an effective SID of approximately 28 mmol/L (after the lactate is metabolized)
226
increased SID metabolic alkalosis ## Footnote Causes fluid tx choice
due to hypernatremia, hypochloremia, or both -- may benefit from a fluid with a low SID such as 0.9% saline (SID = 0)
227
Total weak acids (ATOT) ## Footnote Definition Ions involved
Weak acids are only partially dissociated at physiologic pH. The major contributors to ATOT are albumin and phosphorus -- increases in ATOT = metabolic acidosis -- decreases in ATOT (primarily from decreased albumin) = metabolic alkalosis
228
Strong ion gap
evaluation of unmeasured anions in the SID approach and is similar to the use of anion gap (AG) -- if there are no unmeasured anions (SIG = 0) in the system -- unmeasured anions will cause a more positive value for SIG SIGsimplified = [albumin] × 4.9 – AG SIGsimplified = [albumin] × 7.4 − AG
229
Free water effect | Excess vs deficit
free water effect on BE is due to changes in the water balance -- free water concentration is reflected by sodium concentration -- deficit of free water causing hypernatremia = positive FWE indicating an alkalinizing effect—a contraction alkalosis. -- excess of free water causing hyponatremia = negative FWE indicating an acidotic effect—a dilutional acidosis.
230
Chloride effect
chloride and bicarbonate are reciprocally linked (i.e., when a chloride ion is excreted, a bicarbonate ion is retained and vice versa) -- gastric acid secretion, intestinal bicarbonate secretion, renal acid-base handling, and transcellular ion exchange -- Positive or negative effect
231
Positive Chloride effect
increased (positive) chloride effect (reflecting hypochloremia) is associated with a process that increases bicarbonate concentration and is indicative of an alkalinizing process
232
Negative Chloride effect
decreased chloride effect (negative) marks an acidotic process
233
Albumin effect
Albumin acts as a weak acid and has many H+ binding sites -- Alkalizing effect = Hypoalbuminemia is equivalent to the removal of a weak acid from the system; it will be evident as a positive effect -- Acidifying effect = hyperalbuminemia will be evident as a negative effect, indicating an acidotic influence.
234
Phosphorus effect
Phosphoric and sulfuric acids are products of protein metabolism and are normally excreted by the kidneys. -- AKI or failure retain these acids, resulting in a metabolic acidosis -- Elevated phosphorus will cause a negative effect and indicates an acidotic influence on BE -- hypophosphatemia does not cause a clinically significant alkalosis
235
Lactate effect
-- produced from the conversion of pyruvate by lactate dehydrogenase, a reaction that consumes hydrogen ions -- Acidosis = accumulation of hydrogen ions from the hydrolysis of ATP -- In diseases where mitochondrial function is impaired, such as cellular hypoxia, there is accumulation of both lactate and hydrogen ions leading to lactic acidosis -- elevation = negative effect = acidic influence on BE
236
Lactate definition
* Lactate is an intermediary metabolite of glucose oxidation that serves as a carbohydrate energy substrate reservoir. * it is produced in the cytosol and then either converted back to pyruvate to proceed through local aerobic cellular metabolism or exported out of the cell and transported to distant tissues in the bloodstream * all tissues are capable of producing lactate
237
Glycolysis ## Footnote With Normal O2 present
Glycolysis is the cytosolic process (which occurs in the presence or absence of oxygen) by which **1 mole of glucose** is oxidized to **2 moles of pyruvate**, ATP, and reduced nicotinamide adenine dinucleotide (NADH) -- Glycolysis consumes NAD+ and produces NADH and pyruvate
238
Pyruvate ## Footnote With normal O2 present
With Glycolysis: normal aerobic conditions = only a small quantity of pyruvate is converted into lactate, catalyzed by lactate dehydrogenase (LDH) -- Ultimately lactate is either converted back into pyruvate in local or distant tissues and oxidized to produce energy or converted back into glucose by gluconeogenesis
239
How many moles of ATP is normally produced? ## Footnote with normal O2 present
WITH NORMAL O2 PRESENT = Pyruvate enters the mitochondria and is converted into acetyl CoA, the tricarboxylic acid (TCA) cycle, the electron transport chain, and oxidative phosphorylation to produce **36 moles of ATP**
240
TCA cycle with inadequate O2 available ## Footnote How many ATP mole produced?
To allow glycolysis to continue, NAD+ is replenished and pyruvate and H+ ions are removed by conversion of pyruvate to lactate -- only 2 moles of ATP per glucose molecule,
241
How does lactatic acidosis form?
When the ATP made by glycolysis is utilized, H+ is released into the cytosol -- if oxygen supplies are insufficient, this cannot happen and H+ ions accumulate and are then transported out of the cell. -- acidosis from increased lactate production is mostly due to reduced H+ consumption, not increased lactate production per se.
242
Lactate and Be Relationship
each 1 mmol/L increase in lactate is associated with a concomitant reduction of the standardized base excess of 1 mmol/L.
243
Lacate metabolism
Under conditions of health and aerobiosis, the liver and renal cortex are the predominant lactate-consuming organs -- Hepatic metabolism accounts for 30% to 60% of lactate consumption, and the liver is capable of metabolizing markedly increased lactate loads -- It is reabsorbed by the proximal convoluted tubule, and the renal threshold is 6 to 10 mmol/L.12-14
244
Whole blood lactate measurement
Whole blood lactate refers to the mean of intraerythrocytic and plasma lactate
245
Type A HyperLactatemia
**Increased Oxygen Demand:** * Exercise * Trembling/shivering * Muscle tremors * Seizure activity * Struggling **Decreased Oxygen Delivery:** * Systemic hypoperfusion * Local hypoperfusion * Severe anemia * Severe hypoxemia * Carbon monoxide poisoning
246
Type B1 HyperLactatemia
B1: **Associated with Underlying Disease** * Sepsis * Neoplasia * Diabetes mellitus * Liver disease * Thiamine deficiency * Pheochromocytoma * Hyperthyroidism * Alkalosis
247
Type B2 HyperLactatemia | List as many as you can
B2: **Associated with Drugs or Toxins** * Acetaminophen * Activated charcoal * β2 agonists * Bicarbonate * Corticosteroids * Cyanide * Epinephrine * Ethanol * Ethylene gylcol * Glucose * Insulin * Lactulose * Methanol * Methylxanthines * Nitroprusside * Propofol * Propylene glycol * Salicylates * Strychnine * Sorbitol * TPN * Xylitol
248
Type B3 HyperLactatemia
B3: **Inborn Errors in Metabolism** * Mitochondrial myopathies * Enzymatic deficiencies * MELAS
249
When does HyperLactatemia develop with anemia?
-- Anemia-related hyperlactatemia is highly dependent on intravascular volume status and chronicity -- acute, severe, euvolemic anemia, hyperlactatemia does not develop until the packed cell volume (PCV) drops below 15%.
250
When is HyperLactatemia seen with hypoxemia?
hypoxemia must also be very severe (partial pressure of oxygen [PaO2] 25 to 40 mm Hg) before pure hypoxemia-related hyperlactatemia develops
251
Relationship between hyperlactatemia with hypoperfusion
progressively worsening hypoperfusion shows a fairly linear relationship with plasma lactate concentration
252
Sepsis HyperLactatemia mechanisms
Suggested mechanisms include stimulation of: skeletal muscle Na+/K+-ATPase by catecholamines mitochondrial dysfunction → direct cytochrome inhibition increased hepatic lactate production; reduced hepatic lactate extraction; impaired tissue oxygen extraction and capillary shunting
253
Relationship between glycolysis and hyperlactatemia?
increased aerobic glycolysis secondary to adrenergic stimulation significantly contributes to sepsis-associated hyperlactatemia
254
Neoplasia associated Hyperlactatemia
Hyperlactatemia associated with neoplasia may be due to hypoperfusion in some cases, but malignant cells are known to exhibit atypical carbohydrate metabolism by preferentially utilizing glycolytic pathways for energy production despite sufficient oxygen availability (Warburg effect)
255
How does Epinephrine cause HyperLactatemia
Epinephrine increases Na+/K+-ATPase activity and glycogenolysis resulting in hyperlactatemia -- conditions resulting in excess endogenous catecholamine release, such as pheochromocytoma, have also been associated with hyperlactatemia
256
Dog Breeds reporte to develop Type 3 Hyperlactatemia
Mitochondrial myopathies have been reported in the Jack Russell Terrier, German Shepherd, and Old English Sheepdog -- Pyruvate dehydrogenase deficiency has been recognized in the Clumber Spaniel and Sussex Spaniel
257
Cryptic shock
term cryptic shock has been used to describe ill or injured patients with high lactate concentrations without hypotension
258
D-lactate
D-Lactate is not detected by routine lactate analyzers and can only be measured by specialist laboratories -- Both D- and L-lactate are produced by some bacteria under anaerobic conditions -- In people, D-hyperlactatemia associated with short bowel syndrome and exocrine pancreatic disease is thought to contribute to encephalopathy
259
Correlation between muscle activity and lactate
higher levels of muscle activity can significantly increase lactate (e.g., lots of struggling, trembling, tremors, marked exercise, and seizures).
260
Urine Osmolality
Measurement of urine osmolality and electrolyte concentration can provide valuable insight regarding water balance, effective circulating volume (ECV), and electrolyte and acid-base disorders -- may provide insight into renal handling of water and electrolytes for patients with disturbances in extracellular fluid volume or content -- may be helpful in determining the nature of a patient’s polyuria and evaluating specific serum electrolyte abnormalities -- determining cause for hypoNa+
261
Urine Na+
Assessment of ECV < 20, Decreased ECV (Na avid) Aldosterone presence
262
Urine Cl-
Assessment of ECV Assessment of metabolic alkalosis < 15–25 = Chloride responsive metabolic alkalosis >15–25 = Chloride unresponsive metabolic alkalosis
263
Urine K+
Assessment of Hypokalemia < 15–20 = Nonrenal K loss >40 = Renal K wasting Hyperkalemia >40 = Nonrenal cause (e.g., hypoadrenocorticism)
264
Free water clearance Urine Osmolality
Assessment of solute free water excretion Positive = Free water excretion (absence of ADH secretion and/or response) Negative = Free water retention (ADH secretion and response)
265
total body water
-- continuously in flux because it is being lost through evaporation, elimination, and metabolic processes and gained from food and water intake -- volume and distribution of TBW are under the control of hormonal mechanisms that maintain water and sodium balance by regulating renal water and salt excretion and reabsorption, whereas thirst mechanisms influence water intake
266
Hormone detection of Fluid loss
Loss of fluid with little or no solute (i.e., hypotonic fluid loss) will increase plasma solutes per kilogram water (osmolality). -- increase in the plasma osmolality is detected by the **supraoptic** and **paraventricular** nuclei in the hypothalamus = release of antidiuretic hormone (ADH; arginine vasopressin),
267
Renal conservation of water and sodium is stimulated by:
Hypovolemia stimulates baroreceptors that cause the hypothalamic-pituitary-adrenal axis to produce and release ADH, aldosterone, renin, and cortisol = renal water/Na+ conservation
268
Renal water and sodium excretion is stimulated by:
overexpansion of the cardiovascular system causes stretch of the atria and release of atrial natriuretic peptide = increase in renal water/Na+ excretion
269
Correlation between TBW and body mass
Ninety percent of acute changes in body mass can be attributed to a change in TBW -- 1 kg change in TBW may be equivalent to 1 L change in TBW
270
Interstitial volume changes
examining mucous membrane moisture, skin tent response, eye position, and corneal moisture -- minimum degree of interstitial dehydration that can be detected in the average patient is approximately 5% of body weight -- greater than 12% is likely to be fatal
271
5%–6% Interstitial Dehydration exam findings
Tacky mucous membranes ± some change in skin turgor
272
6%–8% Interstitial Dehydration exam findings
Mild decreased skin turgor Dry mucous membranes
273
8%–10% Interstitial Dehydration exam findings
Obvious decreased skin turgor Retracted globes within orbits
274
10%–12% Interstitial Dehydration exam findings
Persistent skin tent due to complete loss of skin elasticity Dull corneas Evidence of hypovolemia
275
Interstitial overhydration
increased turgor of the skin and subcutaneous tissue, giving it a gelatinous character; peripheral or ventral pitting edema can also occur. Chemosis and clear nasal discharge may also be evident
276
Intravascular volume changes
-- assessed through the examination of perfusion parameters (MM color, capillary refill time, heart rate, and pulse quality) and determination of jugular venous distensibility -- rapid intravascular losses such as hemorrhage can cause hypovolemia without causing clinically detectable changes in the interstitial fluid compartment
277
Intracellular volume changes
cannot be identified on physical examination -- rely on changes in the effective osmolality of ECF (primarily changes in sodium concentration) to mark changes in cell volume -- With decreases in ECF effective osmolality = movement of water into the ICF compartment = increase in intracellular volume -- increases in ECF effective osmolality = decreases in intracellular volume
278
Hypotonic fluid loss ## Footnote How does this occur? what will it cause? what systems does it affect the most?
TBW loss is due to loss of a fluid with little or no salt content (i.e., hypotonic fluid loss) = increases in ECF osmolality, reflected by increases in serum sodium concentration -- water will move from the ICF compartment to the ECF compartment -- loss of ICF volume has the greatest impact on the central nervous system, and if the degree of solute-free water loss is severe and acute it can result in neurologic abnormalities and possibly death as a result of neuronal cell shrinkage ## Footnote Ex: uncontrolled diabetes insipidus
279
Isotonic fluid loss/gain
net loss or gain of fluid with a salt concentration similar to that of the ECF = changes in the ECF volume with little change in ECF osmolality = no change in the ICF volume -- will lead to interstitial dehydration/overhydration -- minimal change in serum sodium concentration with isotonic fluid gain or loss
280
Urine osmolality and urine specific gravity (USG) measurements for ECF hydration status
Urine osmolality and USG will increase as water is reabsorbed from the urine filtrate in states of ECF dehydration -- decrease as water is excreted from the urine in states of ECF over hydration. -- will be limited if the patient has received IV fluid therapy or diuretic administration before urinalysis
281
Fluid objective administration phases: | #4
resuscitation, optimization, stabilization, and evacuation
282
assessment of static dynamic markers for fluid therapy
For example, the caudal vena cava (CVC) diameter and left atrial to aortic root ratio (LA:Ao) are static markers, while the CVC collapsibility index is a dynamic marker (see below)
283
Fluid Challenges Passive Leg Raises
-- mini-boluses of isotonic crystalloids as low as 3–5 ml/kg, administered within 5 minutes -- PLR shifts the volume from the venous system of the legs to the central circulation, mimicking the effect of a fluid bolus. -- may elicit an adrenergic/sympathetic or white coat response in awake companion animals
284
Venous =
right atrial pressure (RAP), and the resistance to venous flow (Rv) are the main driving forces of venous return and can be expressed through the following formula: venous return = (MSFP – RAP/Rv) --other words, venous return can be increased by one of three mechanisms: (1) lowering RAP, (2) decreasing Rv, and (3) increasing MSFP
285
Radiographic assessment of volume status
accuracy of chest radiographs to detect signs of hypo- or hypervolemia through changes in cardiac size, CVC, and pulmonary vessel diameter has been reported at 44% in humans
286
Perfusion parameters
assessed indirectly through upstream and downstream measures of perfusion (e.g., arterial blood pressure and lactate, respectively)
287
Intravenous volume assement: Cardiac POCUS
dogs with clinical signs of hypovolemia have smaller left ventricular and left atrial lumen sizes, and thicker left ventricular walls -- proportional to the severity of hypovolemia -- increased ventricular wall size, and decreased ventricular and atrial lumen size has been observed in cats following volume depletion (7%–10% body weight), while volume administration results in increasing left atrial and ventricular lumen size
288
fluid responsive patient
(A) will increase preload following a fluid bolus, without a significant increase in extravascular lung water (EVLW). As preload increases, stroke volume (SV) will also increase until the optimal preload is achieved. A fluid nonresponsive patient (B) will have a marginal to no increase in preload, and thus no improvement in SV, but a significant increase in EVLW
289
Superimposition of the Frank–Starling and Marik–Phillips curves demonstrating the effects of increasing preload on stroke volume (SV) and lung water in a patient who is preload responsive (a) nonresponsive (b). With sepsis, the extravascular lung water (EVLW) curve is shifted to the left. CO; cardiac output, CVP; central venous pressure
290
Modified Starling’s forces
hydrostatic and colloid osmotic pressure [COP] in the intraluminal and extraluminal spaces) -- govern the magnitude of fluid filtration from the capillary into the interstitial compartment.
291
What % of Albumin accounts for Plasma COP?
plasma albumin accounts for 80% of plasma COP
292
Crystalloids
fluids containing small solutes with molecular weights less than 500 g/mole --readily crosses capillary endothelium and equilibrate throughout the ECF compartment. -- lag time of 20 to 30 minutes for electrolytes to distribute evenly in the extracellular fluid compartments
293
Why is 5% Dextrose in water considered "free water?"
5% dextrose in water is considered free water because after dextrose metabolism it does not contain an effective osmole.
294
How much and how long does a crystalloid volume remain in IVS?
Less than one-third of the volume of crystalloids administered remains in the intravascular space 30 minutes after administration.
295
Tonicity effect on osmotic gradient
lower the fluid tonicity, the greater the dilutional effect on extracellular fluid tonicity, resulting in an osmotic gradient favoring free water movement into the intracellular space and leaving less of the administered fluid volume in the extracellular space.
296
Osmolarity of Isotonic fluids
range of 270 to 310 mOsm/L -- do not cause significant fluid shifts between intracellular and extracellular fluid compartments in normal animals
297
Osmolarity of Hypotonic fluids
0.45% saline has an osmolarity of 154 mOsm/L with a sodium [and chloride] concentration of 77 mEq/L each 5% dextrose in free water is a unique isoosmotic solution (252 mOsm/L) with hypotonic effects since dextrose is rapidly metabolized and free water remains (osmolarity of 0 mOsm/L). ## Footnote Sterile water with an osmolarity of 0 mOsm/L
298
Injectable sterile water adverse effects
should never be administered directly intravenously because of the risk of intravascular hemolysis and endothelial damage
299
Uses for Hypotonic fluids
Hypotonic fluids replenish free water deficits and are useful for treating animals with hypernatremia secondary to hypotonic fluid loss -- distribute throughout both intracellular and extracellular fluid compartments, with less remaining extracellularly in comparison to isotonic fluids
300
Why should you never bolus Hypotonic solutions?
-- rapid IV administration of hypotonic fluids drops plasma and ECF osmolarity (mainly determined by sodium level) quickly; consequently, water shifts from the ECF space to the intracellular space -- may also lead to life-threatening cerebral edema
301
Osmolarity of Hpertonic fluids
7.2% HTS = 2566 mOsm/L
302
Hypertonic solution effects on Free water
-- causes a free water shift (i.e., osmosis) from the intracellular space to the extracellular space, expanding the extracellular fluid volume by 3 to 5 times the volume administered -- Osmotic fluid shifts from the interstitial space into the intravascular space start immediately after intravenous administration of hypertonic solution -- Free water from the intracellular fluid compartment then moves into the extracellular fluid compartment as the interstitial fluid osmolarity rises
303
Uses for Hypertonic fluids
hypovolemic shock, intracranial hypertension, and severe hyponatremia -- It transiently improves CO and tissue perfusion via arteriolar vasodilation (decreased afterload), volume loading (increased preload), and reduced endothelial swelling, and has a weak positive inotropic effect -- improves cerebral perfusion pressure in head trauma patients by augmenting mean arterial blood pressure and decreasing ICP
304
How long is the intravascular volume expansion effect of HTS?
intravascular volume expansion effect of hypertonic saline is transient (< 30 minutes) because of the redistribution of electrolytes throughout the extravascular space and osmotic diuresis
305
Adverse effects of HTS
rates cannot exceed 1 ml/kg/min because hypotension may result from central vasomotor center inhibition or peripheral vasomotor effects mediated by the acute hyperosmolarity (bradycardia and vasodilation).
306
Acid-base effects of crystalloids
acid-base effects of crystalloid administration depend largely on the buffer content of the fluid -- Acetate and lactate are weak buffers included in some crystalloids such as Normosol-R, LRS, and Plasma-Lyte -- Metabolism of these buffers consumes hydrogen ions, resulting in an alkalinizing effect -- beneficial when treating patients with a metabolic acidosis
307
Colloid definition
Colloid solutions contain large hydrophilic molecules (>10,000 Da) that do not readily cross the vascular endothelium and remain within the intravascular space in patients with an uncompromised, intact vascular barrier
308
revised Starling’s equation
Includes endothelial glycocalyx layer, the endothelial basement membrane, and the extracellular matrix to the tradition principle -- subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow
309
traditional Starling’s principle
describes how an increased intravascular to interstitial hydrostatic pressure gradient leads to transvascular fluid flux into the interstitial space at the arteriolar end of the capillary; fluid is subsequently reabsorbed into the intravascular space at venous end of the capillary due to an increased intravascular COP ## Footnote subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow in revised equation
310
Endogenous colloid particles
albumin, globulins, and fibrinogen
311
Synthetic starch colloids
major use of HES solutions is to rapidly expand the intravascular volume with small volume resuscitation by increasing the COP -- HES is synthesized from amylopectin, which is a naturally occurring starch, derived from either potatoes or corn, and is hydroxylated to prevent rapid degradation by α-amylase
312
Natural colloids
fresh frozen plasma (FFP), frozen plasma, cryopoor plasma (CPP), cryoprecipitate (CRYO), human serum albumin (HSA), canine albumin, and intravenous immunoglobulin
313
# DKA When should Phos supplmentation be avoided?
should not be used in conjunction with calcium supplementation. Overzealous phosphate administration can result in iatrogenic hypocalcemia and associated neuromuscular signs, hypernatremia, hypotension, and diffuse tissue calcification
314
Adverse effects of HCO3- supplementation? | #6
1. paradoxical cerebral acidosis, 1. increased carbon dioxide production and the potential for hypercapnia, 1. increased sodium and osmole concentration, risk for circulatory system overload, 1. iatrogenic metabolic alkalosis, 1. changes to the oxygen dissociation curve (Bohr effect), 1. hypokalemia
315
Why is dextrose used with Insulin administration for DKA?
vital to achieve metabolic breakdown of the remaining ketone bodies and resolve acidosis
316
Neuroglycopenia
a shortage of glucose in the brain thereby affecting the function of neurons and altering brain function and behavior. Other subtler signs may include pupil dilation, anxiety, or drooling
317
Hyperosmolar Hyperglycemic State ## Footnote hyperosmolar hyperglycemic non‐ketotic syndrome
characterized by hyperglycemia (blood glucose >600 mg/dL), hyperosmolarity (>350 mOsm/L), and dehydration without the presence of ketoacidosis ## Footnote normal osmolarity in dogs is approximately 290–310 mOsm/L and 290–330 mOsm/L in the cat.
318
Rehydration protocol for Hyperosmolar/Hyperglycemia syndrome
Sodium concentration should be reduced at a rate no greater than 0.5 mEq/L/h to avoid cerebral edema and worsening of neurological status